Ann Nutr Metab 2014;64:239–246 DOI: 10.1159/000365027
Published online: October 2, 2014
Association between Physical Activity in Obese Pregnant Women and Pregnancy Outcomes: The UPBEAT Pilot Study Louise Hayes a Ruth Bell a Steve Robson b Lucilla Poston c on behalf of the UPBEAT Consortium Institutes of a Health and Society and b Cellular Medicine, Newcastle University, Newcastle upon Tyne, and c Division of Women’s Health, Women’s Health Academic Centre, King’s College, London, UK
Abstract Background: Obesity in pregnancy is associated with fetal macrosomia, a raised neonatal fat mass and an increased risk of obesity and poor metabolic health in childhood which persists into adulthood. The offspring of obese women are more likely to be obese than the offspring of lean women when they become pregnant themselves, perpetuating a cycle of obesity and its associated negative metabolic consequences. Increasing physical activity during pregnancy could improve insulin sensitivity and reduce the risk of maternal and offspring adverse outcomes. The UK Pregnancy Better Eating and Activity Trial (UPBEAT) is a trial of a complex intervention designed to improve pregnancy outcomes through dietary changes and physical activity. Data from the pilot trial of 183 women were available for analysis. The relationship between the time spent at different physical activity levels and maternal and infant pregnancy outcomes was examined. Key Messages: Strong evidence exists that physical activity improves insulin sensitivity in non-pregnant populations, and lifestyle interventions of proven effectiveness in non-pregnant populations have been developed.
© 2014 S. Karger AG, Basel 0250–6807/14/0644–0239$39.50/0 E-Mail [email protected] www.karger.com/anm
Women who are active in pregnancy demonstrate better glucose control and favourable pregnancy outcomes. There is a lack of effective interventions to support obese pregnant women to be physically active. Conclusions: No difference was detected in objectively measured physical activity between women randomised to the intervention and control arms of the UPBEAT pilot trial. Light-intensity physical activity was lower in early pregnancy in women who delivered macrosomic infants. Maternal sedentary time at 35–36 weeks’ gestation was positively associated and moderateintensity physical activity was inversely associated with neonatal abdominal circumference. Maternal physical activity is associated with infant birth weight and abdominal circumference and is an appropriate target for intervention to improve infant outcomes. The challenge remains to develop an effective intervention to support obese pregnant women to be physically active. © 2014 S. Karger AG, Basel
Background
The prevalence of obesity in pregnant women is increasing. In the UK, maternal obesity doubled from 7.6 to 15.6% between 1989 and 2007 [1]. This is of concern beLouise Hayes Institute of Health and Society, Newcastle University Baddiley-Clark Building, Richardson Road Newcastle upon Tyne NE2 4AX (UK) E-Mail louise.hayes @ ncl.ac.uk
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Key Words Glucose · Obesity · Offspring · Physical activity · Pregnancy
Developmental Overnutrition
The concept of developmental overnutrition has been proposed as one explanation for the association between maternal BMI and obesity and its sequelae in the offspring of obese mothers [6]. This hypothesis suggests that obese mothers have raised levels of circulating glucose and other nutrients during pregnancy which result in fetal hyperinsulinaemia, stimulating excessive fetal growth. This sets these offspring on a lifetime course of acquisition of excess adipose tissue and poor metabolic health [6]. 240
Ann Nutr Metab 2014;64:239–246 DOI: 10.1159/000365027
Maternal Obesity and Insulin Resistance
The usual increase in insulin resistance that occurs in pregnancy is more pronounced in overweight and obese pregnant women compared to lean pregnant women [8]. Resistance to the action of insulin results in increased lipolysis and leads to a greater availability of glucose and fatty acids to the developing fetus [9], consistent with the theory of developmental overnutrition. The relationships between maternal obesity, an impaired ability to metabolise glucose, and adverse outcomes of pregnancy are well recognised. The association between obesity and the development of GDM is well established [10], as is the link between GDM [11] or impaired glucose tolerance below the threshold for diagnosis of GDM [12] and delivering a baby that is large for gestational age (LGA) and has a higher-than-normal fat mass [13]. Data on exposure to excess circulating glucose in utero and the risk of childhood obesity are sparse; however, in the Pregnancy, Infection and Nutrition (PIN) study of 263 women, a greater than 2-fold risk of being overweight or obese at 3 years of age was identified in the offspring of women with blood glucose levels >130 mg/dl (7.2 mmol/l), following a 1-hour 50-gram glucose challenge test, compared to the offspring of women with blood glucose levels 4 kg at birth were more than twice as likely (OR 2.07; 95% CI 1.91–2.04) to be obese as adults compared to babies weighing ≤4 kg at birth [3]. In a birth cohort of 1,400 individuals followed up at the age of 32 years, maternal pre-pregancy BMI was associated with a worse cardiometabolic profile (higher BMI, waist circumference, and blood pressure and lower HDL cholesterol) in the adult offspring [4]. Interventions to reduce the impact of maternal obesity on adverse pregnancy outcomes have the potential to reap positive benefits not only for the offspring of the index pregnancy but also for subsequent generations born to these offspring. The relative importance of intrauterine exposure for an individual’s predisposition to obesity compared to the role of genetic factors and shared lifestyles during childhood is a subject of increasing interest [5, 6]. It has been reported that the offspring of obese women already display metabolic disturbances at birth, supporting a role of the intrauterine environment in determining future metabolic health. An increasing maternal BMI is associated with higher levels of fat deposition in the abdomen and liver [7], insulin resistance and raised leptin [5] at birth. An understanding of how the intrauterine environment exerts an impact on health that persists through childhood and into adulthood will help to identify appropriate targets for intervention.
Pregnancy
Maternal obesity
Obesity and associated metabolic consequences in adulthood
Raised glucose, insulin, and leptin
Obesity and associated metabolic consequences in childhood
Programming of fetal hypothalamus and neuroendocrine organs
Increased adiposity, insulin resistance, and leptin in the newborn
Macrosomia
Fig. 1. Cycle of maternal obesity and ad-
verse metabolic health among offspring.
compared to their older siblings born before their mother was diagnosed with diabetes [17]. In a study that compared infants who were LGA and born to either a mother that had GDM (and therefore was exposed to higher circulating glucose levels in utero) or a mother that had normal glucose tolerance [18], the prevalence of metabolic syndrome (defined as at least two of the following criteria: obesity, raised blood pressure, raised triglycerides or low HDL) at the age of 11 years was almost twice as high (50%) in LGA infants born to a mother with GDM (n = 42) compared to LGA infants born to a mother with normal glucose tolerance (n = 43; metabolic syndrome prevalence, 29%). These findings are consistent with an effect of maternal glucose on the metabolic health of the offspring that is independent of the birth weight. An opportunity exists for intervention in obese pregnant women to improve insulin sensitivity in order to reduce the negative metabolic consequences associated with maternal insulin resistance that are apparent in the offspring. Physical activity has the potential to offer such an intervention.
The role of physical activity in the prevention and treatment of diabetes in non-pregnant populations is well established. It has been suggested that physical activity helps to prevent diabetes and to improve glucose control in individuals with diabetes because it improves insulin sensitivity [19]. For example, in the European Relationship between Insulin Sensitivity and Cardiovascular risk (RISC) study, in which physical activity was measured objectively in 800 individuals, a strong relationship between total physical activity and insulin sensitivity was found [19]. Lifestyle interventions, which include a physical activity component, are effective in reducing the incidence of diabetes in high-risk populations. For example, a systematic review of pharmacological and lifestyle interventions to reduce the incidence of type 2 diabetes in individuals with impaired glucose tolerance concluded that lifestyle interventions achieved a reduction in the risk of diabetes of 49%, compared to a reduction of 30% for pharmaco-
Physical Activity in Obese Pregnant Women
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Physical Activity and Insulin Resistance
Physical Activity and Glucose Metabolism in Pregnancy
A number of observational studies have reported an association between higher levels of physical activity in pre-pregnancy and early pregnancy and a lower prevalence of GDM. A meta-analysis that pooled data from 8 studies, including pre-pregnancy physical activity data on 34,929 women and early pregnancy physical activity data on 4,401 women, concluded that being in the highest pre-pregnancy physical activity category was associated with a greater than 50% reduction in risk of GDM, and for early pregnancy physical activity it was associated with a reduction of 25% [22]. An acute effect of physical activity (treadmill walking) on blood glucose concentrations in pregnancy was observed in 46 women in a study examining the impact of different intensities and durations of exercise on glucose [23]. The study authors found an interaction between the estimated risk of GDM and the glucose response to exercise and concluded that walking for 25 min at a vigorous intensity (70% of the heart rate reserve) or 35–40 min at a moderate intensity (30% of the heart rate reserve) achieved a substantial decrease (approx. 1.0 mmol/l) in the glucose concentration in women considered to be at a high risk for GDM (defined as: a history of GDM/ PCOS, a family history of diabetes, overweight/obesity, a history of macrosomia or early weight gain in the current pregnancy). Evidence is beginning to accumulate that improved insulin sensitivity, achieved through physical activity during pregnancy, could translate into favourable outcomes for the offspring. A recent observational study assessed physical activity in 30 pregnant women at 28–32 weeks’ gestation, using a combined heart rate monitor and accelerometer, and estimated insulin sensitivity using the Matsuda composite model [24]. The body com242
Ann Nutr Metab 2014;64:239–246 DOI: 10.1159/000365027
position of the offspring of these women was measured at 11–19 weeks post-partum using air displacement plethysmography (PeaPod). Infant fat-free mass was significantly related to both maternal insulin sensitivity and maternal physical activity. The authors of the study concluded that insulin sensitivity at 28–32 weeks’ gestation was related to a favourable body fat distribution in the offspring and that this relationship appeared to be influenced by maternal physical activity [24]. This finding, if confirmed in larger studies, provides justification for offering interventions to support pregnant women to be active and thereby improve the health of their offspring. Interventions to increase physical activity in obese women during pregnancy could improve insulin sensitivity and reduce the exposure of the developing fetus to excess glucose and insulin and thus help to reduce the burden of obesity and metabolic disturbances among the offspring.
Physical Activity during Pregnancy
Until relatively recently, pregnant women were discouraged from being physically active. As recently as 1985, the American Congress of Obstetrics and Gynaecology (ACOG) recommended that pregnant women ‘stringently limit the type, duration and intensity of their exercise to minimize both fetal and maternal risk’. Current guidance from ACOG and other national bodies now recommends that all pregnant women, including those with a raised BMI, are encouraged to participate in regular moderate-intensity physical activity for 30 min on all or most days of the week. This change in guidance reflects accumulating evidence that physical activity during pregnancy confers benefits to both the mother and the offspring. Data from the Health Survey for England 2008 show that only 29% of (non-pregnant) women reported meeting this guideline, and that objective measurement of physical activity revealed that as few as 4% of women actually met the guideline [25]. Most women, therefore, are insufficiently active at the beginning of pregnancy. Generally, physical activity declines with gestation. For example, a recent study found that the number of steps walked per day, assessed using a pedometer, fell by 1,340 steps (equivalent to walking approx. 1,000 m) between 12 and 28 weeks’ gestation in 97 women at high risk for developing GDM [26]. There is a need, therefore, for interventions to support women to be active during pregnancy.
Hayes et al.
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logical interventions [20]. It has been demonstrated that when women were randomised to a weight loss intervention in which weight loss was achieved by either calorie restriction of 500 kcal/day or energy expenditure of 500 kcal/day through exercise for a 14-week period a significant improvement in glucose disposal was achieved in the exercise group but not in the calorie restriction group [21]. Both groups achieved a similar weight loss (approx. 8 kg), suggesting that physical activity has a role in improving insulin sensitivity that is independent of weight loss.
Physical Activity in Obese Pregnant Women
Ann Nutr Metab 2014;64:239–246 DOI: 10.1159/000365027
Despite convincing observational data demonstrating that physical activity during pregnancy is associated with better glucose control and lower GDM prevalence, evidence from intervention studies demonstrating a positive impact of physical activity on pregnancy outcomes is sparse, leading some authors to suggest that a focus on diet-based rather than physical-activity interventions for pregnant women is warranted [27]. A number of trials of physical-activity interventions to improve glucose control during pregnancy have reported disappointing results. For example, in a trial in which 855 pregnant women were randomised to receive either an exercise programme or standard care, no difference in the prevalence of GDM at 32–36 weeks was found [28]. However, in that study, as in others reporting negative findings, compliance with the physical-activity intervention was poor (only 55% of the women followed the protocol). This suggests that what is being demonstrated is a failure of interventions to have an impact on physical activity, rather than a failure of physical activity to have an impact on glucose homeostasis. Evidence exists that when good adherence to a physical-activity intervention is attained, a positive impact on glucose control is achieved. For example, in 2 studies in which women were randomised to a supervised physical-activity intervention consisting of 3 supervised sessions per week, women in the intervention arm had significantly lower blood glucose levels than women in the control arm at 28 weeks’ gestation [29, 30].
The UK Pregnancies Better Eating and Activity Trial
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To date, most intervention studies in obese women have been carried out in a small number of women and have not been of adequate size to address clinical outcomes. Several trials have been undertaken recently, or are planned, to assess the impact of lifestyle interventions on relevant clinical outcomes in overweight and obese women, such as GDM and delivery of an LGA infant, as well as longer-term health outcomes of the offspring. These include the LIMIT randomised trial of 2,212 overweight and obese pregnant women, which recently reported no differences in delivery of an LGA infant (the primary outcome) or maternal outcomes between women who received a lifestyle intervention and women in the control arm of the study [31]. Women who received the lifestyle intervention, however, were less likely to deliver a macrosomic (>4,000 g) infant.
The UK Pregnancies Better Eating and Activity Trial (UPBEAT) is an ongoing randomised controlled trial (RCT) of a combined physical activity and dietary intervention in over 1,500 obese (BMI ≥30) pregnant women, which aims to improve glucose homeostasis and thereby prevent GDM (the primary outcome) (trial registration No. ISRCTN89971375). A pilot RCT in 183 women to determine if the intervention led to changes in physical activity and diet was completed in 2011 [32]. Research Ethics Committee approval was obtained for the trial (UK Integrated Research Application System reference 09/ H08-2/5), and all participants provided written informed consent to participate in the trial. Details of how physical activity was measured have been reported previously [32]. Briefly, physical activity was assessed by an ActiGraph accelerometer worn for 7 consecutive days at baseline (16+0–18+6 weeks’ gestation), 27+0–28+6 weeks’ gestation, and 35+0–36+6 weeks’ gestation and via a questionnaire (Recent Physical Activity Questionnaire, RPAQ). For accelerometry, a valid recording day was defined as >500 min of monitored ‘on’ time in 24 h, and women providing at least 3 valid days of data were included in the analysis. Recorded times were categorised as sedentary [SED; 4,000 g. SED was recorded using an accelerometer at 1,952 cpm. a After a GDM diagnosis.
Maternal fasting glucose SED 0.162 LPA –0.117 MVPA –0.070 Maternal 2-hour glucose SED 0.101 LPA –0.169 MVPA –0.046 Newborn abdominal circumference SED –0.287* LPA –0.036 MVPA –0.101
28 weeks (n = 43)
36 weeks (n = 34)
0.090 –0.224* –0.078
– – –
0.132 –0.225* –0.114
– – –
–0.920 0.024 –0.011
0.435* –0.367* –0.466*
* Statistically significant correlation (p < 0.05).
statistical significance. LPA at 28 weeks’ gestation was negatively associated with fasting and 2-hour post-challenge glucose. The relationship between maternal physical activity and newborn abdominal circumference, as a proxy for abdominal adiposity, was also examined (table 2). Maternal SED time at baseline was negatively associated with newborn abdominal circumference, but at 36 weeks’ gestation the relationship was positive. LPA and MVPA at 36 weeks’ gestation were negatively associated with newborn abdominal circumference.
er baseline SED and a lower LPA and MVPA in women who developed GDM, but these differences were not statistically significant (table 1). Twenty-nine women gave birth to a macrosomic (>4,000 g) baby, and for whom valid physical activity data were available in 26 cases. LPA at baseline, but not MVPA, was significantly lower in women who delivered a macrosomic baby compared to those who did not (158 min/day compared to 186 min/ day; p = 0.014). The correlations between maternal physical activity and fasting and 2-hour post-75-gram OGTT are presented in table 2. A trend towards baseline SED being weakly positively associated and LPA being negatively associated with fasting and post-challenge glucose levels was observed, but the relationships did not reach 244
Ann Nutr Metab 2014;64:239–246 DOI: 10.1159/000365027
Maternal obesity is associated with an increased risk of obesity and an unfavourable cardiometabolic profile in the offspring, which persists into adulthood and therefore impacts future generations. Obese women are more insulin resistant than lean women during pregnancy and thus the offspring of obese women are exposed to higher levels of glucose and other nutrients in utero. Exposure to intrauterine overnutrition is associated with a higher birth weight, increased adiposity and indicators of poor metabolic health. Physical activity during pregnancy has the potential to increase insulin sensitivity and improve the health of the offspring. Data presented here from the UPBEAT pilot trial and from other studies [23, 30, 34] demonstrate that Hayes et al.
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Discussion
References
Physical Activity in Obese Pregnant Women
information they received was too basic and that attending group sessions was too time-consuming [32]. Refinement of the protocol for the delivery of the intervention in the UPBEAT trial has been made in view of these findings, although the intervention remains the same. Previous work has also found that pregnant women report a lack of time and childcare, as well as physical discomfort, as barriers to physical activity [32]. The intervention design needs to address these barriers by considering flexibility in the mode and location of intervention delivery, and in terms of facilitating engagement in appropriate types of activity. In summary, it is increasingly acknowledged that efforts to prevent obesity and its associated poor health should begin in utero [7] and should aim to improve maternal glucose control as this reduces the risk of obesity among offspring [16]. Physical activity is an appropriate target for intervention to achieve this. The identification of methods by which obese pregnant women can best be supported to be sufficiently active remains a challenge which is worth addressing.
Acknowledgements We thank the study research team and the health trainers and all the pregnant women who participated in the UPBEAT pilot study. This report presents independent research commissioned by the National Institute for Health Research (NIHR) under Programme Grants for Applied Research programme No. RP-040710452. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.
Disclosure Statement The authors have no conflicts of interest to declare.
1 Heslehurst N, et al: A nationally representative study of maternal obesity in England, UK: trends in incidence and demographic inequalities in 619 323 births, 1989–2007. Int J Obes 2010;34:420–428. 2 Dodd JM, et al: Maternal and perinatal health outcomes by body mass index category. Aust NZ J Obstet Gynaecol 2011;51:136–140. 3 Yu ZB, et al: Birth weight and subsequent risk of obesity: a systematic review and meta-analysis. Obes Rev 2011;12:525–542.
4 Hochner H, et al: Associations of maternal prepregnancy body mass index and gestational weight gain with adult offspring cardiometabolic risk factors: the Jerusalem Perinatal Family Follow-up Study. Circulation 2012; 125:1381–1389. 5 Catalano PM, et al: Fetuses of obese mothers develop insulin resistance in utero. Diabetes Care 2009;32:1076–1080. 6 Lawlor DA: The Society for Social Medicine John Pemberton Lecture 2011: developmental overnutrition – an old hypothesis with new importance? Int J Epidemiol 2013;42:7–29.
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physical activity during pregnancy is associated with improved maternal glucose control and less macrosomia and adiposity in the offspring [24]. Specifically in the UPBEAT pilot study, even LPA in obese women was associated with improved glucose tolerance and a lower infant abdominal circumference. It was of particular interest to note that more time spent on sedentary activities and less time spent on light and moderate intensity physical activity at 36 weeks’ gestation were related to an increasing infant abdominal circumference, whereas physical activity when measured at 28 weeks showed no such relationships. Should this observation be repeated in the larger cohort of the full RCT, in fully adjusted regression analyses, it could indicate that physical activity towards term may have specific benefits for reducing adiposity in the child. Despite the existence of lifestyle interventions of proven effectiveness to increase physical activity and improve insulin sensitivity in non-pregnant populations, there is a paucity of interventions with demonstrated effectiveness for pregnant women. Many intervention studies targeting physical activity in pregnant women, including the UPBEAT pilot trial, have failed to impact physical activity levels. Despite the difficulty of designing effective interventions to support obese pregnant women to be physically active on the basis of this and other studies, it is clearly premature to abandon efforts to do so [35]. In the context of the increasing problem of obesity internationally, the potential benefits that could be achieved if obese pregnant women become sufficiently active are substantial. A better understanding of the barriers to obese women engaging in physical activity during pregnancy is needed to inform the development of interventions. Process evaluation of the UPBEAT pilot trial revealed that the intervention was considered acceptable and well received by most women, although some reported that the lifestyle
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27 Thangaratinam S, et al: Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence. BMJ 2012;344:e2088. 28 Stafne SN, et al: Regular exercise during pregnancy to prevent gestational diabetes: a randomized controlled trial. Obstet Gynecol 2012;119:29–36. 29 Barakat R, et al: Exercise during pregnancy improves maternal glucose screen at 24–28 weeks: a randomised controlled trial. Br J Sports Med 2012;46:656–661. 30 Ong MJ, et al: Supervised home-based exercise may attenuate the decline of glucose tolerance in obese pregnant women. Diabetes Metab 2009;35:418–421. 31 Dodd JM, et al: Antenatal lifestyle advice for women who are overweight or obese: LIMIT randomised trial. BMJ 2014;348:g1285. 32 Poston L, et al: Developing a complex intervention in obese pregnant women: assessment of behavioural change and process evaluation through a randomised controlled exploratory trial. BMC Pregnancy Childbirth 2013;13:148. 33 International Association of Diabetes and Pregnancy Study Groups Consensus Panel: International Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010; 33:676–682. 34 Barakat R, et al: Exercise during pregnancy improves maternal health perception: a randomized controlled trial. Am J Obstet Gynecol 2011;204:402.e1–402.e47. 35 Poston L, Chappell LC: How should women be advised on weight management in pregnancy? BMJ 2012;344:e2774.
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7 Modi N, et al: The influence of maternal body mass index on infant adiposity and hepatic lipid content. Pediatr Res 2011;70:287–291. 8 Endo S, et al: Differences in insulin sensitivity in pregnant women with overweight and gestational diabetes mellitus. Gynecol Endocrinol 2006;22:343–349. 9 Nelson SM, Matthews P, Poston L: Maternal metabolism and obesity: modifiable determinants of pregnancy outcome. Hum Reprod Update 2010;16:255–275. 10 National Collaborating Centre for Women’s and Children’s Health: Diabetes in Pregnancy: NICE Clinical Guideline. London, RCOG Press, 2008. 11 Metzger BE, et al: Summary and recommendations of the Fifth International WorkshopConference on Gestational Diabetes Mellitus. Diabetes Care 2007; 30(suppl 2):S251–S260, erratum in Diabetes Care 2007;30:3154. 12 HAPO Study Cooperative Research Group: Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008;358:1991–2002. 13 Hapo Study Cooperative Research Group: Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: associations with neonatal anthropometrics. Diabetes 2009; 58: 453–459. 14 Deierlein AL, et al: The association between maternal glucose concentration and child BMI at age 3 years. Diabetes Care 2011; 34: 480–484. 15 Remmers F, Delemarre-van de Waal HA: Developmental programming of energy balance and its hypothalamic regulation. Endocr Rev 2011;32:272–311. 16 Chandler-Laney PC, et al: Maternal glucose concentration during pregnancy predicts fat and lean mass of prepubertal offspring. Diabetes Care 2011;34:741–745.
Published online: October 2, 2014
Association between Physical Activity in Obese Pregnant Women and Pregnancy Outcomes: The UPBEAT Pilot Study Louise Hayes a Ruth Bell a Steve Robson b Lucilla Poston c on behalf of the UPBEAT Consortium Institutes of a Health and Society and b Cellular Medicine, Newcastle University, Newcastle upon Tyne, and c Division of Women’s Health, Women’s Health Academic Centre, King’s College, London, UK
Abstract Background: Obesity in pregnancy is associated with fetal macrosomia, a raised neonatal fat mass and an increased risk of obesity and poor metabolic health in childhood which persists into adulthood. The offspring of obese women are more likely to be obese than the offspring of lean women when they become pregnant themselves, perpetuating a cycle of obesity and its associated negative metabolic consequences. Increasing physical activity during pregnancy could improve insulin sensitivity and reduce the risk of maternal and offspring adverse outcomes. The UK Pregnancy Better Eating and Activity Trial (UPBEAT) is a trial of a complex intervention designed to improve pregnancy outcomes through dietary changes and physical activity. Data from the pilot trial of 183 women were available for analysis. The relationship between the time spent at different physical activity levels and maternal and infant pregnancy outcomes was examined. Key Messages: Strong evidence exists that physical activity improves insulin sensitivity in non-pregnant populations, and lifestyle interventions of proven effectiveness in non-pregnant populations have been developed.
© 2014 S. Karger AG, Basel 0250–6807/14/0644–0239$39.50/0 E-Mail [email protected] www.karger.com/anm
Women who are active in pregnancy demonstrate better glucose control and favourable pregnancy outcomes. There is a lack of effective interventions to support obese pregnant women to be physically active. Conclusions: No difference was detected in objectively measured physical activity between women randomised to the intervention and control arms of the UPBEAT pilot trial. Light-intensity physical activity was lower in early pregnancy in women who delivered macrosomic infants. Maternal sedentary time at 35–36 weeks’ gestation was positively associated and moderateintensity physical activity was inversely associated with neonatal abdominal circumference. Maternal physical activity is associated with infant birth weight and abdominal circumference and is an appropriate target for intervention to improve infant outcomes. The challenge remains to develop an effective intervention to support obese pregnant women to be physically active. © 2014 S. Karger AG, Basel
Background
The prevalence of obesity in pregnant women is increasing. In the UK, maternal obesity doubled from 7.6 to 15.6% between 1989 and 2007 [1]. This is of concern beLouise Hayes Institute of Health and Society, Newcastle University Baddiley-Clark Building, Richardson Road Newcastle upon Tyne NE2 4AX (UK) E-Mail louise.hayes @ ncl.ac.uk
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Key Words Glucose · Obesity · Offspring · Physical activity · Pregnancy
Developmental Overnutrition
The concept of developmental overnutrition has been proposed as one explanation for the association between maternal BMI and obesity and its sequelae in the offspring of obese mothers [6]. This hypothesis suggests that obese mothers have raised levels of circulating glucose and other nutrients during pregnancy which result in fetal hyperinsulinaemia, stimulating excessive fetal growth. This sets these offspring on a lifetime course of acquisition of excess adipose tissue and poor metabolic health [6]. 240
Ann Nutr Metab 2014;64:239–246 DOI: 10.1159/000365027
Maternal Obesity and Insulin Resistance
The usual increase in insulin resistance that occurs in pregnancy is more pronounced in overweight and obese pregnant women compared to lean pregnant women [8]. Resistance to the action of insulin results in increased lipolysis and leads to a greater availability of glucose and fatty acids to the developing fetus [9], consistent with the theory of developmental overnutrition. The relationships between maternal obesity, an impaired ability to metabolise glucose, and adverse outcomes of pregnancy are well recognised. The association between obesity and the development of GDM is well established [10], as is the link between GDM [11] or impaired glucose tolerance below the threshold for diagnosis of GDM [12] and delivering a baby that is large for gestational age (LGA) and has a higher-than-normal fat mass [13]. Data on exposure to excess circulating glucose in utero and the risk of childhood obesity are sparse; however, in the Pregnancy, Infection and Nutrition (PIN) study of 263 women, a greater than 2-fold risk of being overweight or obese at 3 years of age was identified in the offspring of women with blood glucose levels >130 mg/dl (7.2 mmol/l), following a 1-hour 50-gram glucose challenge test, compared to the offspring of women with blood glucose levels 4 kg at birth were more than twice as likely (OR 2.07; 95% CI 1.91–2.04) to be obese as adults compared to babies weighing ≤4 kg at birth [3]. In a birth cohort of 1,400 individuals followed up at the age of 32 years, maternal pre-pregancy BMI was associated with a worse cardiometabolic profile (higher BMI, waist circumference, and blood pressure and lower HDL cholesterol) in the adult offspring [4]. Interventions to reduce the impact of maternal obesity on adverse pregnancy outcomes have the potential to reap positive benefits not only for the offspring of the index pregnancy but also for subsequent generations born to these offspring. The relative importance of intrauterine exposure for an individual’s predisposition to obesity compared to the role of genetic factors and shared lifestyles during childhood is a subject of increasing interest [5, 6]. It has been reported that the offspring of obese women already display metabolic disturbances at birth, supporting a role of the intrauterine environment in determining future metabolic health. An increasing maternal BMI is associated with higher levels of fat deposition in the abdomen and liver [7], insulin resistance and raised leptin [5] at birth. An understanding of how the intrauterine environment exerts an impact on health that persists through childhood and into adulthood will help to identify appropriate targets for intervention.
Pregnancy
Maternal obesity
Obesity and associated metabolic consequences in adulthood
Raised glucose, insulin, and leptin
Obesity and associated metabolic consequences in childhood
Programming of fetal hypothalamus and neuroendocrine organs
Increased adiposity, insulin resistance, and leptin in the newborn
Macrosomia
Fig. 1. Cycle of maternal obesity and ad-
verse metabolic health among offspring.
compared to their older siblings born before their mother was diagnosed with diabetes [17]. In a study that compared infants who were LGA and born to either a mother that had GDM (and therefore was exposed to higher circulating glucose levels in utero) or a mother that had normal glucose tolerance [18], the prevalence of metabolic syndrome (defined as at least two of the following criteria: obesity, raised blood pressure, raised triglycerides or low HDL) at the age of 11 years was almost twice as high (50%) in LGA infants born to a mother with GDM (n = 42) compared to LGA infants born to a mother with normal glucose tolerance (n = 43; metabolic syndrome prevalence, 29%). These findings are consistent with an effect of maternal glucose on the metabolic health of the offspring that is independent of the birth weight. An opportunity exists for intervention in obese pregnant women to improve insulin sensitivity in order to reduce the negative metabolic consequences associated with maternal insulin resistance that are apparent in the offspring. Physical activity has the potential to offer such an intervention.
The role of physical activity in the prevention and treatment of diabetes in non-pregnant populations is well established. It has been suggested that physical activity helps to prevent diabetes and to improve glucose control in individuals with diabetes because it improves insulin sensitivity [19]. For example, in the European Relationship between Insulin Sensitivity and Cardiovascular risk (RISC) study, in which physical activity was measured objectively in 800 individuals, a strong relationship between total physical activity and insulin sensitivity was found [19]. Lifestyle interventions, which include a physical activity component, are effective in reducing the incidence of diabetes in high-risk populations. For example, a systematic review of pharmacological and lifestyle interventions to reduce the incidence of type 2 diabetes in individuals with impaired glucose tolerance concluded that lifestyle interventions achieved a reduction in the risk of diabetes of 49%, compared to a reduction of 30% for pharmaco-
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Physical Activity and Insulin Resistance
Physical Activity and Glucose Metabolism in Pregnancy
A number of observational studies have reported an association between higher levels of physical activity in pre-pregnancy and early pregnancy and a lower prevalence of GDM. A meta-analysis that pooled data from 8 studies, including pre-pregnancy physical activity data on 34,929 women and early pregnancy physical activity data on 4,401 women, concluded that being in the highest pre-pregnancy physical activity category was associated with a greater than 50% reduction in risk of GDM, and for early pregnancy physical activity it was associated with a reduction of 25% [22]. An acute effect of physical activity (treadmill walking) on blood glucose concentrations in pregnancy was observed in 46 women in a study examining the impact of different intensities and durations of exercise on glucose [23]. The study authors found an interaction between the estimated risk of GDM and the glucose response to exercise and concluded that walking for 25 min at a vigorous intensity (70% of the heart rate reserve) or 35–40 min at a moderate intensity (30% of the heart rate reserve) achieved a substantial decrease (approx. 1.0 mmol/l) in the glucose concentration in women considered to be at a high risk for GDM (defined as: a history of GDM/ PCOS, a family history of diabetes, overweight/obesity, a history of macrosomia or early weight gain in the current pregnancy). Evidence is beginning to accumulate that improved insulin sensitivity, achieved through physical activity during pregnancy, could translate into favourable outcomes for the offspring. A recent observational study assessed physical activity in 30 pregnant women at 28–32 weeks’ gestation, using a combined heart rate monitor and accelerometer, and estimated insulin sensitivity using the Matsuda composite model [24]. The body com242
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position of the offspring of these women was measured at 11–19 weeks post-partum using air displacement plethysmography (PeaPod). Infant fat-free mass was significantly related to both maternal insulin sensitivity and maternal physical activity. The authors of the study concluded that insulin sensitivity at 28–32 weeks’ gestation was related to a favourable body fat distribution in the offspring and that this relationship appeared to be influenced by maternal physical activity [24]. This finding, if confirmed in larger studies, provides justification for offering interventions to support pregnant women to be active and thereby improve the health of their offspring. Interventions to increase physical activity in obese women during pregnancy could improve insulin sensitivity and reduce the exposure of the developing fetus to excess glucose and insulin and thus help to reduce the burden of obesity and metabolic disturbances among the offspring.
Physical Activity during Pregnancy
Until relatively recently, pregnant women were discouraged from being physically active. As recently as 1985, the American Congress of Obstetrics and Gynaecology (ACOG) recommended that pregnant women ‘stringently limit the type, duration and intensity of their exercise to minimize both fetal and maternal risk’. Current guidance from ACOG and other national bodies now recommends that all pregnant women, including those with a raised BMI, are encouraged to participate in regular moderate-intensity physical activity for 30 min on all or most days of the week. This change in guidance reflects accumulating evidence that physical activity during pregnancy confers benefits to both the mother and the offspring. Data from the Health Survey for England 2008 show that only 29% of (non-pregnant) women reported meeting this guideline, and that objective measurement of physical activity revealed that as few as 4% of women actually met the guideline [25]. Most women, therefore, are insufficiently active at the beginning of pregnancy. Generally, physical activity declines with gestation. For example, a recent study found that the number of steps walked per day, assessed using a pedometer, fell by 1,340 steps (equivalent to walking approx. 1,000 m) between 12 and 28 weeks’ gestation in 97 women at high risk for developing GDM [26]. There is a need, therefore, for interventions to support women to be active during pregnancy.
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logical interventions [20]. It has been demonstrated that when women were randomised to a weight loss intervention in which weight loss was achieved by either calorie restriction of 500 kcal/day or energy expenditure of 500 kcal/day through exercise for a 14-week period a significant improvement in glucose disposal was achieved in the exercise group but not in the calorie restriction group [21]. Both groups achieved a similar weight loss (approx. 8 kg), suggesting that physical activity has a role in improving insulin sensitivity that is independent of weight loss.
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Despite convincing observational data demonstrating that physical activity during pregnancy is associated with better glucose control and lower GDM prevalence, evidence from intervention studies demonstrating a positive impact of physical activity on pregnancy outcomes is sparse, leading some authors to suggest that a focus on diet-based rather than physical-activity interventions for pregnant women is warranted [27]. A number of trials of physical-activity interventions to improve glucose control during pregnancy have reported disappointing results. For example, in a trial in which 855 pregnant women were randomised to receive either an exercise programme or standard care, no difference in the prevalence of GDM at 32–36 weeks was found [28]. However, in that study, as in others reporting negative findings, compliance with the physical-activity intervention was poor (only 55% of the women followed the protocol). This suggests that what is being demonstrated is a failure of interventions to have an impact on physical activity, rather than a failure of physical activity to have an impact on glucose homeostasis. Evidence exists that when good adherence to a physical-activity intervention is attained, a positive impact on glucose control is achieved. For example, in 2 studies in which women were randomised to a supervised physical-activity intervention consisting of 3 supervised sessions per week, women in the intervention arm had significantly lower blood glucose levels than women in the control arm at 28 weeks’ gestation [29, 30].
The UK Pregnancies Better Eating and Activity Trial
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To date, most intervention studies in obese women have been carried out in a small number of women and have not been of adequate size to address clinical outcomes. Several trials have been undertaken recently, or are planned, to assess the impact of lifestyle interventions on relevant clinical outcomes in overweight and obese women, such as GDM and delivery of an LGA infant, as well as longer-term health outcomes of the offspring. These include the LIMIT randomised trial of 2,212 overweight and obese pregnant women, which recently reported no differences in delivery of an LGA infant (the primary outcome) or maternal outcomes between women who received a lifestyle intervention and women in the control arm of the study [31]. Women who received the lifestyle intervention, however, were less likely to deliver a macrosomic (>4,000 g) infant.
The UK Pregnancies Better Eating and Activity Trial (UPBEAT) is an ongoing randomised controlled trial (RCT) of a combined physical activity and dietary intervention in over 1,500 obese (BMI ≥30) pregnant women, which aims to improve glucose homeostasis and thereby prevent GDM (the primary outcome) (trial registration No. ISRCTN89971375). A pilot RCT in 183 women to determine if the intervention led to changes in physical activity and diet was completed in 2011 [32]. Research Ethics Committee approval was obtained for the trial (UK Integrated Research Application System reference 09/ H08-2/5), and all participants provided written informed consent to participate in the trial. Details of how physical activity was measured have been reported previously [32]. Briefly, physical activity was assessed by an ActiGraph accelerometer worn for 7 consecutive days at baseline (16+0–18+6 weeks’ gestation), 27+0–28+6 weeks’ gestation, and 35+0–36+6 weeks’ gestation and via a questionnaire (Recent Physical Activity Questionnaire, RPAQ). For accelerometry, a valid recording day was defined as >500 min of monitored ‘on’ time in 24 h, and women providing at least 3 valid days of data were included in the analysis. Recorded times were categorised as sedentary [SED; 4,000 g. SED was recorded using an accelerometer at 1,952 cpm. a After a GDM diagnosis.
Maternal fasting glucose SED 0.162 LPA –0.117 MVPA –0.070 Maternal 2-hour glucose SED 0.101 LPA –0.169 MVPA –0.046 Newborn abdominal circumference SED –0.287* LPA –0.036 MVPA –0.101
28 weeks (n = 43)
36 weeks (n = 34)
0.090 –0.224* –0.078
– – –
0.132 –0.225* –0.114
– – –
–0.920 0.024 –0.011
0.435* –0.367* –0.466*
* Statistically significant correlation (p < 0.05).
statistical significance. LPA at 28 weeks’ gestation was negatively associated with fasting and 2-hour post-challenge glucose. The relationship between maternal physical activity and newborn abdominal circumference, as a proxy for abdominal adiposity, was also examined (table 2). Maternal SED time at baseline was negatively associated with newborn abdominal circumference, but at 36 weeks’ gestation the relationship was positive. LPA and MVPA at 36 weeks’ gestation were negatively associated with newborn abdominal circumference.
er baseline SED and a lower LPA and MVPA in women who developed GDM, but these differences were not statistically significant (table 1). Twenty-nine women gave birth to a macrosomic (>4,000 g) baby, and for whom valid physical activity data were available in 26 cases. LPA at baseline, but not MVPA, was significantly lower in women who delivered a macrosomic baby compared to those who did not (158 min/day compared to 186 min/ day; p = 0.014). The correlations between maternal physical activity and fasting and 2-hour post-75-gram OGTT are presented in table 2. A trend towards baseline SED being weakly positively associated and LPA being negatively associated with fasting and post-challenge glucose levels was observed, but the relationships did not reach 244
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Maternal obesity is associated with an increased risk of obesity and an unfavourable cardiometabolic profile in the offspring, which persists into adulthood and therefore impacts future generations. Obese women are more insulin resistant than lean women during pregnancy and thus the offspring of obese women are exposed to higher levels of glucose and other nutrients in utero. Exposure to intrauterine overnutrition is associated with a higher birth weight, increased adiposity and indicators of poor metabolic health. Physical activity during pregnancy has the potential to increase insulin sensitivity and improve the health of the offspring. Data presented here from the UPBEAT pilot trial and from other studies [23, 30, 34] demonstrate that Hayes et al.
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Discussion
References
Physical Activity in Obese Pregnant Women
information they received was too basic and that attending group sessions was too time-consuming [32]. Refinement of the protocol for the delivery of the intervention in the UPBEAT trial has been made in view of these findings, although the intervention remains the same. Previous work has also found that pregnant women report a lack of time and childcare, as well as physical discomfort, as barriers to physical activity [32]. The intervention design needs to address these barriers by considering flexibility in the mode and location of intervention delivery, and in terms of facilitating engagement in appropriate types of activity. In summary, it is increasingly acknowledged that efforts to prevent obesity and its associated poor health should begin in utero [7] and should aim to improve maternal glucose control as this reduces the risk of obesity among offspring [16]. Physical activity is an appropriate target for intervention to achieve this. The identification of methods by which obese pregnant women can best be supported to be sufficiently active remains a challenge which is worth addressing.
Acknowledgements We thank the study research team and the health trainers and all the pregnant women who participated in the UPBEAT pilot study. This report presents independent research commissioned by the National Institute for Health Research (NIHR) under Programme Grants for Applied Research programme No. RP-040710452. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.
Disclosure Statement The authors have no conflicts of interest to declare.
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physical activity during pregnancy is associated with improved maternal glucose control and less macrosomia and adiposity in the offspring [24]. Specifically in the UPBEAT pilot study, even LPA in obese women was associated with improved glucose tolerance and a lower infant abdominal circumference. It was of particular interest to note that more time spent on sedentary activities and less time spent on light and moderate intensity physical activity at 36 weeks’ gestation were related to an increasing infant abdominal circumference, whereas physical activity when measured at 28 weeks showed no such relationships. Should this observation be repeated in the larger cohort of the full RCT, in fully adjusted regression analyses, it could indicate that physical activity towards term may have specific benefits for reducing adiposity in the child. Despite the existence of lifestyle interventions of proven effectiveness to increase physical activity and improve insulin sensitivity in non-pregnant populations, there is a paucity of interventions with demonstrated effectiveness for pregnant women. Many intervention studies targeting physical activity in pregnant women, including the UPBEAT pilot trial, have failed to impact physical activity levels. Despite the difficulty of designing effective interventions to support obese pregnant women to be physically active on the basis of this and other studies, it is clearly premature to abandon efforts to do so [35]. In the context of the increasing problem of obesity internationally, the potential benefits that could be achieved if obese pregnant women become sufficiently active are substantial. A better understanding of the barriers to obese women engaging in physical activity during pregnancy is needed to inform the development of interventions. Process evaluation of the UPBEAT pilot trial revealed that the intervention was considered acceptable and well received by most women, although some reported that the lifestyle
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